Stroke, Volume 56, Issue Suppl_1, Page AWP270-AWP270, February 1, 2025. Introduction:Patients experiencing a transient ischemic attack (TIA) or minor stroke have a high long-term risk of subsequent stroke that persists for over one year following presentation. While risk stratification tools like the ABCD2score have been used to identify patients at high risk of stroke in the short-term (within the first 90 days), less is known about factors that determine long-term risk. Some studies suggest that traditional predictors of early stroke risk may not be associated with long-term risk, while others have reported conflicting results. We aimed to summarize the association between clinical, demographic, imaging factors and the long-term risk of stroke in patients experiencing TIA or minor stroke.Methods:We searched MEDLINE, Embase, and the Web of Science from inception to June 2024, for observational studies that examined factors associated with subsequent stroke in patients experiencing TIA or minor stroke during a minimum follow-up of one year. Two reviewers independently performed study screening and data extraction. For the primary analysis, we included prognostic factors if they were derived from a multivariable Cox proportional hazards model and reported in at least 2 studies. We contacted the corresponding authors of the studies to obtain adjusted effect estimates when these values could not be extracted from the reported data. We conducted random effects meta-analyses of adjusted hazard ratios and report pooled effect estimates with 95% confidence intervals.Results:Of 13051 citations identified, we included 28 studies examining 85,328 patients including unpublished data from 8 studies that we directly obtained from study authors. Factors associated with an increased risk of stroke at one year or beyond included male sex, older age, hypertension, diabetes mellitus, atrial fibrillation, history of stroke or TIA before the qualifying event, history of coronary artery disease, presence of hemiparesis, aphasia, baseline ABCD2score of 4 or greater, acute infarct on brain imaging, large-artery atherosclerosis, and cardioembolism (Figure 1).Conclusion:We have identified important prognostic factors associated with long-term risk of stroke after a TIA or minor stroke. These findings provide a framework for evidence-based risk stratification of patients who may require extended treatment and vigorous monitoring.
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Clinical effectiveness and implementation outcomes of pMDI-to-DPI switch in children between 5 and 12 years of age: a scoping review protocol
Introduction
Inhalers are critical in asthma treatment, and inappropriate inhaler use leads to poor asthma outcomes. In adults and adolescents, dry powder inhalers (DPIs) are safe and effective alternatives to mainstay pressurised metered dose inhalers and could bridge the asthma care gap while also reducing the environmental burden of asthma care. Despite being licensed for use in ages 5 years old and older, the evidence for clinical effectiveness is less clear for patients between ages 5 and 12 years. This protocol describes a scoping review. The primary aim of the review is to identify and synthesise evidence on the clinical effectiveness of DPI use in children aged 5–12 years old with asthma and other wheezing conditions. The secondary aim of the review is to outline the implementation strategies and outcomes supporting the prescribing or switching to DPIs in children.
Methods and analysis
We will conduct a systematic and comprehensive literature search across four electronic databases (Medline, Embase, Cochrane Library and CINAHL) and grey literature. Screening and data extraction will be done independently by two review authors with discrepancies resolved through consensus. Data will be extracted and charted by two independent reviewers, then presented diagrammatically or tabulated with an accompanying narrative summary.
Ethics and dissemination
Ethical approval was not required for this study as it is a scoping review. The results of this scoping review will be submitted to a peer-reviewed scientific journal for publication.
Understanding the impact of racism on surgical outcomes in settler nation-states USA and Canada: a protocol for a systematic review and meta-analysis
Introduction
To improve surgical quality and safety, health systems must prioritise equitable care for surgical patients. Racialised patients experience worse postoperative outcomes when compared with non-racialised surgical patients in settler colonial nation-states. Identifying preventable adverse outcomes for equity-deserving patient populations is an important starting point to begin to address these gaps in care. To derive literature-based estimates of the outcome gap for racialised surgical patients, we will systematically review and meta-analyse rates of adverse postoperative events associated with common and/or high-risk operations performed in Canada and the USA.
Methods and analysis
An electronic search of Medline, Embase, Web of Science, Cochrane Central, CINAHL and Scopus will be conducted to identify studies reviewing complication rates of racialised compared with non-racialised patients from inception to December 2023. We will include publications from the USA and Canada comparing surgical outcomes of racialised and non-racialised patients. The procedures of interest will be the four most common (hip arthroplasty, knee arthroplasty, appendectomy and cholecystectomy), and the five highest risk (oesophagectomy, abdominal aortic aneurysm, aortic valve replacement, coronary artery bypass graft and pancreatectomy) surgical procedures performed in these countries. The outcomes will be mortality, length of stay in hospital, readmission, reoperation, wound dehiscence, surgical site infection, pulmonary embolism, sepsis or septic shock, pneumonia, blood transfusion, stroke, myocardial infarction and bile duct injury. Summary estimates of cumulative incidence, prevalence, incidence rate and occurrence rate of complications using DerSimonian and Laird random effects models will be calculated for the systematic review and meta-analysis. Heterogeneity in these estimates will be examined using subgroup analyses and meta-regression.
Ethics and dissemination
This study uses secondary data and, therefore, does not require ethics approval. This study will be communicated through presentations at international conferences and published in peer-reviewed literature. The results from this study will inform the development of future surgical equity tools and quality improvement programmes and provide benchmarks on the impact of racism on surgical outcomes.
PROSPERO registration number
CRD42024491439.
Barriers and facilitators to improved sedentary behaviour in coronary heart disease patients: a scoping review
Introduction
The majority of patients with coronary heart disease (CHD) are at high sedentary levels, which severely affects patient prognosis and outcome. Despite the proven benefits of reducing sedentary behaviour (SB), intervention studies’ effectiveness has been limited. Thus, the factors influencing SB change in patients with CHD need to be explored. This scoping review aimed to identify barriers and facilitators to improved SB in CHD patients and map these factors to the Capability–Opportunity–Motivation-Behaviour model.
Methods
We conducted a scoping review in accordance with the Arksey and O’Malley framework. Eligibility criteria included qualitative and quantitative studies on SB in patients with CHD. Nine databases were searched (PubMed, Medline, Embase, CINAHL, Web of Science Core Collection, Scopus, CNKI, WanFang and VIP) from inception through 31 December 2023, following the scoping review methodology.
Results
A total of 24 studies, including two qualitative and 22 quantitative studies, were included, with 15 847 patients. Barriers to improved SB in CHD patients included capability (eg, physical characteristics, lack of knowledge to improve SB), opportunity (eg, lack of partnership support, lack of resources to carry out activities) and motivation (eg, maintaining the habit of SB, impaired belief in activities). Facilitators included capability (eg, exercise session, improving understanding of SB), opportunity (eg, utilisation of support, tele-rehabilitation guidance, diversification of living environments) and motivation (perceived benefit).
Conclusions
Patients with CHD have unique barriers and facilitators to improving SB. Future research should adequately reduce barriers and promote facilitators to increase the effectiveness of interventions.
Successful open defecation-free intervention in low- and middle-income countries: a qualitative synthesis systematic review protocol
Introduction
The results of open defecation-free (ODF) programmes vary greatly, especially in low- and middle-income countries (LMICs). This study will systematically investigate available qualitative research to identify the elements contributing to open defecation programmes’ effectiveness in various situations across LMICs. Furthermore, this review seeks to identify gaps in the available literature and areas that require additional investigation and action.
Methods and analysis
Inclusion criteria were developed considering issues related to open defecation in LMICs, sanitation interventions and behavioural change. Research examining sanitation interventions in schools, shelters, disability communities and virtual communities was excluded, as the review focused exclusively on community-based interventions. Studies published in English and Indonesian were included without limitation of the initial year until 31 January 2025. Systematic research will be carried out using ScienceDirect, PubMed, ProQuest and Scopus databases. Information from grey literature, including conference proceedings and reports from relevant organisations, will be systematically searched using Google Scholar and the websites of leading institutions, such as the WHO, UNICEF and WaterAid. This systematic review did not impose any restrictions on the place and date of publication. Two reviewers followed Joanna Briggs Institute guidelines in selecting studies, conducting critical appraisal using confidential tools and extracting data using a structured approach. Data synthesis will be performed using meta-aggregate methods to identify the themes. A ConQual Summary will be used to assess confidence in the findings.
Ethics and dissemination
The findings of the systematic review will be disseminated through a publication in a peer-reviewed journal and presented at a relevant conference. Since the data used will not contain individual patient information, ethical approval is unnecessary.
PROSPERO registration number
CRD42023408851.
Analytical approaches to evaluate risk factors of multimorbidity: a systematic scoping review protocol
Introduction
Understanding causal risk factors that contribute to the development of multimorbidity is essential for designing and targeting effective preventive strategies. Despite a large body of research in this field, there has been little critical discussion about the appropriateness of the various analytical approaches used. This proposed scoping review aims to summarise and appraise the analytical approaches used in the published literature that evaluated risk factors of multimorbidity and to provide guidance for researchers conducting analyses in this field.
Methods and analysis
We will systematically search three electronic databases—Embase, Global Health and MEDLINE, as well as the reference lists of identified relevant review articles, from inception to September 2024. We will screen titles and abstracts using the artificial intelligence-aided software ASReview, followed by screening for eligible articles in full text and extracting data. We will then categorise the analytical approaches used across studies, provide a comprehensive overview of the methodology and discuss the potential strengths and limitations of each analytical approach.
Ethics and dissemination
We will undertake a secondary analysis of published literature; therefore, ethical approval is not required. The results will be disseminated through an open-access, peer-reviewed publication. This systematic scoping review will serve as a guide for researchers in selecting analytical approaches for aetiological multimorbidity research, thereby improving the quality and comparability of research in this field.
Clinicopathological and prognostic significance of the microcystic elongated and fragmented pattern in endometrial cancer: a systematic review and meta-analysis
Objective
The presence of the microcystic elongated and fragmented (MELF) pattern, distinguished by its microcystic, elongated and fragmented attributes, constitutes a common manifestation of myometrial invasion (MI) within endometrial carcinoma. However, the prognostic significance of this pattern has not been definitively established. Consequently, this research aimed to clarify the prognostic implications of the MELF pattern for individuals diagnosed with endometrial carcinoma.
Design
Systematic review and meta-analysis of observational clinical studies.
Data sources
An extensive review of the literature was conducted using reputable databases such as PubMed, Embase, Web of Science and the Cochrane Library, covering the period from January 2003 to October 2023. Search terms encompassed endometrial cancer and the MELF pattern.
Eligibility criteria for selecting studies
The inclusion criteria were patients who had undergone hysterectomy and whose pathology confirmed endometrial endometrioid carcinoma, with or without MELF infiltration.
Data extraction and synthesis
Two reviewers performed data extraction separately. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Stata V.17.0 software was used for statistical analysis.
Results
The meta-analysis incorporated 16 retrospective cohort studies. Employing a fixed-effects approach, the analysis demonstrated an association of the MELF pattern with reduced overall survival (HR 2.21, 95% CI 1.50–3.25, p=0.000) and lower disease-free survival rates among patients with endometrial cancer (HR 1.72, 95% CI 1.17 to 2.55, p=0.006). Furthermore, aggregated data revealed a linkage between the MELF pattern and significant MI, nodal metastasis, involvement of the lymphovascular space, penetration of the cervical stroma and progression to advanced stages of endometrial carcinoma.
Conclusion
The MELF pattern serves as a significant adverse prognostic factor in endometrial cancer, warranting increased attention.
Facilitators and barriers to parental involvement in neonatal pain management in the NICU: a scoping review
Objectives
Neonatal pain prevention is not only a humanistic but also an ethical imperative. Fitting with the principles of family-centred care, parental involvement in neonatal pain management plays an active role in infant development and parental well-being. However, the process of parental involvement faces constant challenges. To help structure and implement a family engagement programme in neonatal pain management in the neonatal intensive care unit (NICU), we conducted a scoping review to identify facilitators and barriers to parental involvement in neonatal pain management.
Methods
We conducted the scoping review using the Arksey and O’Malley framework. PubMed, Cochrane Library, Web of Science, CINAHL, Scopus, Wanfang database (Chinese), CNKI (Chinese), VIP database(Chinese) and SinoMed (Chinese) were searched systematically for relevant studies published in English and Chinese from inception up to October 2023. We categorised the facilitators and barriers based on the socioecological model and analysed the results thematically in each category.
Results
Ten English qualitative studies were included in the final analysis. The 34 facilitators and 41 barriers extracted were grouped into 4 domains of the socioecological model framework. Of the 10 facilitator themes, the most critical theme was informational and emotional support. Of the 10 barrier themes, the most frequently reported theme was restricted policies and resources.
Conclusions
Our review highlights the essential roles of intrapersonal and interpersonal factors in parental involvement in pain management while suggesting the interconnectedness of factors in various domains within the context of the socioecological model. It implies that most interventions require development and administration at both intrapersonal and interpersonal levels. Regarding the macrolevel, a broad programme with clear regulatory approaches and targeted guidelines could be developed in the future to drive innovations in NICU pain management mode.
Synovial biomarkers in the diagnosis of post-traumatic osteoarthritis following anterior cruciate ligament and meniscus injuries: protocol for a systematic review
Introduction
This review aims to synthesise research evidence regarding biomarkers in the synovial fluid that may predict the risk of post-traumatic osteoarthritis (PTOA) in young adults. Considering the high prevalence of knee joint injuries, particularly among youth sports athletes, this review will focus on anterior cruciate ligament and/or meniscal ruptures. These injuries are highly associated with PTOA, with studies indicating that even with surgical reconstruction, 50%–80% of affected individuals develop knee PTOA within a 10-year follow-up.
Methods and analysis
The results of this systematic review will be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Diagnostic Test Accuracy guidelines. Comprehensive electronic searches will be conducted across five platforms: four bibliographic databases (PubMed, Cochrane Central Register of Controlled Trials, Web of Science Core Collection and Embase) and ClinicalTrials.gov registry. These searches will use combinations of predefined keywords, such as “knee”, “synovial fluid”, “post-traumatic osteoarthritis”, “anterior cruciate ligament”, “meniscus”, “trauma”, “inflammation” and “biomarker”. We will include randomised clinical trials, non-randomised prospective or retrospective clinical studies, case controls, cohort studies and case series, ranging from database inception to 30 June 2024 and published in English. Two independent reviewers will screen and evaluate the retrieved studies to determine their eligibility. Any reviewer disagreements will be resolved through discussion and consensus or, if necessary, by consultation with a third reviewer. The data will be extracted from the included studies and analysed, with the risk of bias assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. A narrative synthesis will be performed to evaluate the strength and consistency of the findings, considering both the methodological quality of the included studies and the reliability of the results.
Ethics and dissemination
Ethical approval is not required for this review as it is a secondary study based on public and published data. The findings from this work will be submitted for publication in a peer-reviewed journal and presented at relevant academic conferences. Any amendments to the protocol arising from deviations during the study’s execution will be documented and reported in the final publication.
PROSPERO registration number
CRD42024534272.
Prevalence of musculoskeletal disorders among garment workers: a systematic review and meta-analysis
Background
Garment workers are at high risk of musculoskeletal disorders (MSDs) due to repetitive physical tasks, long working hours and varying workstations. As there is no existing epidemiological overview of MSDs among garment workers, this systematic review aimed to evaluate the global evidence on prevalence of MSDs in this population.
Methods
A systematic review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medline, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus and Web of Science electronic databases were searched to identify studies published in English up to November 2022. Random-effects meta-analysis was used to estimate pooled prevalence.
Results
The search yielded 258 published studies, of which 14 were deemed relevant and were included in this review. The included studies reported prevalence from India (n=3), Bangladesh (n=2), Ethiopia (n=2), Thailand (n=2), Botswana (n=1), Iran (n=1), Sri Lanka (n=1), Cambodia (n=1) and Denmark (n=1) and involved 15 029 garment workers. Most of the included studies (79%) were assessed to be methodologically sound (low risk of bias). The mean age of participants ranged from 24.2 to 40 years. The prevalence of MSDs ranged from 15.5% to 92%. The pooled prevalence of MSDs from nine studies was 65.6% (95% CI 44.5% to 51.9%). Low back pain and neck pain were reported as the common MSDs in the included studies.
Conclusions
The findings highlight the considerable risk of MSDs, especially low back and neck pain, linked to repetitive tasks, extended hours and inconsistent workstations. Given the heavy toll of MSDs on this workforce, targeted interventions and ergonomic improvements are crucial to mitigate the risks and improve garment workers’ well-being.
Social inclusion programming for older adults living in age-friendly cities: a scoping review
Objectives
Creating age-friendly cities (AFCs) is essential for supporting older adults’ well-being. The WHO’s 2007 guide outlines key features of AFCs, including social inclusion. Despite increasing numbers of AFC programmes, diverse experiences of ageing are often overlooked. This scoping review explores innovative programmes implemented by AFCs to enhance social inclusion for older adults.
Design
A scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.
Data sources
Systematic searches were conducted between December 2023 and January 2024 across relevant databases (Ovid Medline, OVID Embase, OVID PsycINFO, CINAHL, Web of Science, Cochrane Library and Scopus) and the grey literature.
Eligibility criteria for selecting studies
Selection criteria included English language publications describing evaluated age-friendly, social inclusion programmes for older adults.
Data extraction and synthesis
Data extraction followed Gonyea and Hudson’s (2015) framework assessing programmes on population, environment and/or sector inclusion levels. Inductive analysis identified and evaluated aspects of social inclusion.
Results
We identified 20 peer-reviewed publications and 18 grey literature sources. Most programmes (peer review, n=19, 95.0%; grey, n=18, 100.0%) addressed population inclusion, incorporated environment (peer review, n=10, 50.0%; grey, n=15, 83.3%) and/or sector inclusion (peer review, n=7, 35.0%; grey, n=15, 83.3%). Key outcomes included an improved sense of belonging, increased engagement with community resources and activities, enhanced digital literacy and connectivity, and a reduction in feelings of loneliness and isolation. A notable gap was the absence of studies focused on Indigenous populations.
Conclusion
We highlight that programmes addressing population, environment and sectoral inclusion may improve the well-being of older adults in urban settings. Our findings will inform AFC practices and policies by deepening our understanding of how social inclusion can be improved for older adults, including those from under-represented groups, ensuring an equitable approach to enhancing quality of life.
[Corrigendum] Corrigendum for “The global birth prevalence of clubfoot: a systematic review and meta-analysis”
In Table 2 (Study characteristics and estimated birth prevalence) and Fig. 2 (Pooled global birth prevalence of clubfoot), the estimate was noted as 3.57 (2.93–4.34) per 1000 births. However, Zhou et al. (2020) report this as per 10,000 births. The correct estimate is therefore 0.36 (0.29–0.43) per 1000 births.
Adherence to tuberculosis (TB) treatment in high compared to low TB burden countries: study protocol for a systematic review and meta-analysis with a qualitative meta-synthesis of themes
Introduction
Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries. Additionally, it seeks to identify the unique facilitators and barriers to treatment adherence in these distinct settings.
Methods and analysis
This systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Statement. Using key medical subject heading terms and free-text terms related to TB treatment adherence, a systematic search of the literature will be performed in Medline, Embase, CINAHL, Scopus, Global Health and the Cochrane Databases of Systematic Reviews. A medical librarian will assist with developing the search strategy. Two independent reviewers will independently screen studies against predefined inclusion and exclusion criteria at both the title/abstract and full-text stages. Working in duplicate, the same two reviewers will independently extract relevant study and outcomes data, including study descriptors, TB burden, adherence levels and adherence measures, from eligible studies. Countries will be classified according to TB burden based on the WHO’s high-burden country list from the post-2015 era (2015–2025). The quality of the included studies will be appraised using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. Qualitative data will be appraised using the Critical Appraisal Skills Programme tool. Studies will be pooled using the DerSimonian-Laird random-effects meta-analysis. Additionally, a meta-synthesis of the qualitative data from the included studies may be conducted to identify emergent themes related to facilitators and barriers of TB treatment adherence in high- vs low-TB burden countries.
Ethics and dissemination
Ethics approval is not required for this study as it does not involve the recruitment or collection of data from participants. The findings from this systematic review and meta-analysis will be disseminated through publication in peer-reviewed journals, presentations at scientific conferences, and via social media channels to enhance visibility, particularly within programmatic and policy spheres.
PROSPERO registration number
CRD42021273336
How do socioeconomic inequalities and preterm birth interact to modify health and education outcomes? A narrative systematic review
Objectives
How are socioeconomic inequalities modified by, or how do they interact with, preterm birth?
Design
Narrative systematic review of quantitative observational studies of an interaction, or effect modification, between preterm birth and socioeconomic status.
Data sources
Five databases were searched for studies published between January 2000 and June 2020. Title and abstract were reviewed to identify articles for dual screening. All included studies were citation searched.
Eligibility criteria
Inclusion criteria were comparison across socioeconomic status and gestational age, interaction between the two, or stratification by either, and health or education as outcome.
Data extraction and synthesis
Data extracted included study design, sample size, outcome, interaction measure, effect and significance. Included studies were assessed for methodological quality and synthesised narratively.
Results
After searches, 52 studies were identified for full-text screening and, with supplementary citation searches, we identified 21 included studies. Eighteen studies studied interaction between gestational age or preterm birth, and socioeconomic status. Three groups of outcomes were identified: cognitive, mental health and developmental. Age at outcome measurement was divided into four categories: preschool, primary school (5–11), secondary school (11–18) and post school (18–29). Seven studies found a significant interaction between the effect of preterm birth and socioeconomic status. Six of these interactions demonstrate that the negative influence of low socioeconomic status was stronger for those born preterm (and vice versa) for cognitive and mental health outcomes, all in studies with a sample size of more than 100 000. One study found that negative effects of low socioeconomic status were reduced for those born preterm (and vice versa) for communication delay.
Conclusions
Our findings suggest that the impact of low socioeconomic status on cognitive and mental health outcomes is exacerbated by preterm birth. The remaining evidence suggests the effects are not modified; however, this is potentially due to underpowered studies. Public health action is indicated to support babies born preterm, particularly for disadvantaged families, to improve educational attainment and mental health.
PROSPERO registration number
CRD42020203613.
Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening
Background
Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20–24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign. Consequently, many individuals receive extra imaging and/or unnecessary procedures, which can have a negative physical and psychological impact, as well as placing a financial burden on health systems. Therefore, there is a need to identify individuals who need no interval CT between screening rounds.
Methods and analysis
The aim of this study is to identify risk factors predictive of LC, which are known at the time of the scan, in patients with LDCT screen-detected lung nodules. The MEDLINE and EMBASE databases will be searched and articles that are on cohorts or mention cohorts of screenees with nodules will be identified. A data extraction framework will ensure consistent extraction across studies. Individual participant data (IPD) will be collected to perform a one-stage IPD meta-analysis using hierarchical univariate models. Clustering will be accounted for by having separate intercept terms for each cohort. Where IPD is not available, the effects of risk factors will be extracted from publications, if possible. Effects from IPD cohorts and aggregate data will be reported and compared. The PROBAST (Prediction model Risk Of Bias ASsessment Tool) will be used for assessment of quality of the studies.
Ethics and dissemination
Ethical approval was not required as this study is a secondary analysis. The results will be disseminated through publication in peer-reviewed journals and presentations at relevant conferences.
PROSPERO registration number
CRD42022309515
Global insight into rare disease and orphan drug definitions: a systematic literature review
Objectives
This study sheds light on the available global definitions, classifications, and criteria used for rare diseases (RDs), ultrarare diseases (URDs), orphan drugs (ODs) and ultraorphan drugs (UODs) and provides insights into the rationale behind these definitions.
Design
A systematic literature review was conducted to identify existing definitions and the criteria used to define RDs, ODs and their subtypes.
Data sources
Searches were performed in the PubMed/Medline, Embase, Scopus and Web of Science (Science and Social Sciences Citation Index) databases covering articles published from 1985 to 2021.
Eligibility criteria for selecting studies
English-language studies on the general human population were included if they provided definitions or criteria for RDs, ODs and/or their subtypes without restrictions on publication year, country or jurisdiction.
Data extraction and synthesis
Two independent reviewers conducted the search, screening and data extraction. Narrative synthesis, content analysis and descriptive analyses were conducted to extract and categorise definitions and criteria from these sources. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.
Results
Online searches identified 2712 published articles. Only 93 articles met the inclusion criteria, with 209 distinct definitions extracted. Specifically, 93 of these articles pertained to 119 RDs, 11 URDs, 67 ODs and 12 UODs. These definitions varied in their reliance on prevalence based and other contextual criteria.
Conclusion
Prevalence-based criteria alone pose challenges, as disease frequencies differ by country. Establishing country-specific definitions can enhance understanding, support intercountry evaluations, improve healthcare efficiency and access to ODs, and strengthen equity and equality in healthcare. Such efforts would also promote research and development and support better outcomes for patients with complex and rare conditions.
PROSPERO registration number
CRD42021252701.